The specific area of research of this proposal concerns possible interactions between mercury compounds and certain selenium- containing compounds, such as sodium selenite. The latter have been shown to antagonize the effects of mercury compounds in animal toxicity studies as well as in cytotoxicity studies in cell cultures. However, the mechanism by which this antagonism occurs remains unclear. We have previously carried out studies to ascertain the effects of sodium selenite and selenate by themselves on nucleic acid synthesis by intact cells, isolated nuclei, and purified polymerases. The purpose of this project is to examine the ability of these compounds to antagonize the effects of mercury compounds on nucleic acid synthesis in these systems. During the first project period we focused on the ability of selenite to antagonize the inhibitory effects of mercury compounds on the DNA and RNA polymerases. During the course of these studies we observed that inhibition of DNA and RNA polymerases by sodium selenite is potentiated by sulfhydryl compounds, as a result of the formation of selenotrisulfide derivatives. This laboratory is currently involved in a project whose aim is to characterize this phenomenon, and to relate it to the inhibitory effect of selenite on DNA synthesis in intact cells and isolated nuclei. The aim of the specific project in which the students will be involved during the coming project period is to examine the possible role of these selenotrisulfides in the antagonism by selenite of the effects of mercury compounds. Specifically the ability of these compounds to antagonize the inhibitory effects of mercury compounds on nucleic acid synthesis by DNA and RNA polymerases and by isolated nuclei, will be examined.